RESUMEN
Background: Direct oral anticoagulants (DOACs) have demonstrated clinical benefits and better patient adherence over low-molecular-weight heparin (LMWH) in treating patients with cancer-associated venous thrombosis (CAT). We aimed to compare the cost-effectiveness of DOACs against LMWH in patients with CAT from the perspective of the Hong Kong healthcare system. Methods: A Markov state-transition model was performed to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) for DOACs and LMWH in a hypothetical cohort of 10,000 patients with CAT over a 5-year lifetime horizon. The model was primarily based on the health states of no event, recurrent venous thromboembolism, bleeding, and death. Transition probabilities, relative risks, and utilities were derived from the literature. Resource cost data were obtained from the Hong Kong Hospital Authority. Deterministic and probabilistic sensitivity analyses tested the robustness of the results. Results: Relative to LMWH, DOACs were associated with increased QALYs (1.52 versus 1.50) at a lower medical cost of USD 2,232 versus 8,224 in five years. The cost of LMWH was the main contributor to the outcome. Out of 10,000 simulated cases, DOACs were dominant in 15.8% and cost-effective in 42.1%, at the willingness-to-pay threshold of USD 148,392 per additional QALY. Conclusions: DOACs were associated with greater QALY improvements and lower overall costs compared to LMWH. Accounting for uncertainty, DOACs were between cost-effective and dominant in 57.9% of cases. DOACs are a cost-effective alternative to LMWH in the management of CAT in Hong Kong.
RESUMEN
Given the existing uncertainty regarding the effectiveness and safety of switching from low-molecular-weight heparin (LMWH) to direct oral anticoagulants (DOACs) in patients with cancer-associated venous thrombosis (CAT), we conducted a comprehensive population-based cohort study utilizing electronic health database in Hong Kong. A total of 4356 patients with CAT between 2010 and 2022 were included, with 1700 (39.0%) patients switching to DOAC treatment. Compared to continuous LMWH treatment, switching to DOACs was associated with a significantly lower risk of hospitalization due to venous thromboembolism (HR: 0.49 [95% CI = 0.35-0.68]) and all-cause mortality (HR: 0.67 [95% CI = 0.61-0.74]), with no significant difference in major bleeding (HR: 1.04 [95% CI = 0.83-1.31]) within six months. These findings provide reassurance regarding the effectiveness and safety of switching from LMWH to DOACs among patients with CAT, including vulnerable patient groups.
Asunto(s)
Anticoagulantes , Hemorragia , Heparina de Bajo-Peso-Molecular , Neoplasias , Trombosis de la Vena , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Trombosis de la Vena/tratamiento farmacológico , Administración Oral , Hong Kong/epidemiología , Hemorragia/inducido químicamente , Resultado del Tratamiento , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Estudios de Cohortes , Hospitalización/estadística & datos numéricos , Sustitución de Medicamentos , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Venlafaxine dose regimens vary considerably between individuals, requiring personalized dosing. AIM: This study aimed to identify dose-related influencing factors of venlafaxine through real-world data analysis and to construct a personalized dose model using advanced artificial intelligence techniques. METHOD: We conducted a retrospective study on patients with depression treated with venlafaxine. Significant variables were selected through a univariate analysis. Subsequently, the predictive performance of seven models (XGBoost, LightGBM, CatBoost, GBDT, ANN, TabNet, and DT) was compared. The algorithm that demonstrated optimal performance was chosen to establish the dose prediction model. Model validation used confusion matrices and ROC analysis. Additionally, a dose subgroup analysis was conducted. RESULTS: A total of 298 patients were included. TabNet was selected to establish the venlafaxine dose prediction model, which exhibited the highest performance with an accuracy of 0.80. The analysis identified seven crucial variables correlated with venlafaxine daily dose, including blood venlafaxine concentration, total protein, lymphocytes, age, globulin, cholinesterase, and blood platelet count. The area under the curve (AUC) for predicting venlafaxine doses of 75 mg, 150 mg, and 225 mg were 0.90, 0.85, and 0.90, respectively. CONCLUSION: We successfully developed a TabNet model to predict venlafaxine doses using real-world data. This model demonstrated substantial predictive accuracy, offering a personalized dosing regimen for venlafaxine. These findings provide valuable guidance for the clinical use of the drug.
Asunto(s)
Inteligencia Artificial , Relación Dosis-Respuesta a Droga , Medicina de Precisión , Clorhidrato de Venlafaxina , Humanos , Clorhidrato de Venlafaxina/administración & dosificación , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Medicina de Precisión/métodos , Anciano , Antidepresivos de Segunda Generación/administración & dosificación , Depresión/tratamiento farmacológicoRESUMEN
BACKGROUND: Venlafaxine is frequently prescribed for patients with depression. To control the concentration of venlafaxine within the therapeutic window for the best treatment effect, a model to predict venlafaxine concentration is necessary. AIM: Our objective was to develop a prediction model for venlafaxine concentration using real-world evidence based on machine learning and deep learning techniques. METHOD: Patients who underwent venlafaxine treatment between November 2019 and August 2022 were included in the study. Important variables affecting venlafaxine concentration were identified using a combination of univariate analysis, sequential forward selection, and machine learning techniques. Predictive performance of nine machine learning and deep learning algorithms were assessed, and the one with the optimal performance was selected for modeling. The final model was interpreted using SHapley Additive exPlanations. RESULTS: A total of 330 eligible patients were included. Five influential variables that affect venlafaxine concentration were venlafaxine daily dose, sex, age, hyperlipidemia, and adenosine deaminase. The venlafaxine concentration prediction model was developed using the eXtreme Gradient Boosting algorithm (R2 = 0.65, mean absolute error = 77.92, root mean square error = 93.58). In the testing cohort, the accuracy of the predicted concentration within ± 30% of the actual concentration was 73.49%. In the subgroup analysis, the prediction accuracy was 69.39% within the recommended therapeutic range of venlafaxine concentration within ± 30% of the actual value. CONCLUSION: The XGBoost model for predicting blood concentration of venlafaxine using real-world evidence was developed, guiding the adjustment of regimen in clinical practice.
Asunto(s)
Aprendizaje Automático , Clorhidrato de Venlafaxina , Clorhidrato de Venlafaxina/farmacocinética , Clorhidrato de Venlafaxina/uso terapéutico , Clorhidrato de Venlafaxina/administración & dosificación , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Adulto , Antidepresivos de Segunda Generación/farmacocinética , Depresión/tratamiento farmacológicoRESUMEN
BACKGROUND AND AIM: Proton pump inhibitors (PPIs) may increase the risk of COVID-19 among non-vaccinated subjects via various mechanisms, including gut dysbiosis. We aimed to investigate whether PPIs also affect the clinical outcomes of COVID-19 among vaccine recipients. METHODS: This was a territory-wide cohort study of 3 272 286 vaccine recipients (aged ≥ 18 years) of ≥ 2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior gastrointestinal surgery, immunocompromised status, and prior COVID-19. The primary outcome was COVID-19, and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Covariates include age, sex, the Charlson Comorbidity Index, comorbidities, and concomitant medication use. Subjects were followed from index date (first dose of vaccination) until outcome occurrence, death, additional dose of vaccination, or March 31, 2022. Exposure was pre-vaccination PPI use (any prescription within 90 days before the index date). Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with PPI use. RESULTS: Among 439 154 PS-matched two-dose vaccine recipients (mean age: 65.3 years; male: 45.7%) with a median follow-up of 6.8 months (interquartile range: 2.6-7.9), PPI exposure was associated with a higher risk of COVID-19 (aIRR: 1.08; 95% confidence interval [95% CI]: 1.05-1.10), hospitalization (aIRR: 1.20; 95% CI: 1.08-1.33), and severe infection (aIRR: 1.57; 95% CI: 1.24-1.98). Among 188 360 PS-matched three-dose vaccine recipients (mean age: 62.5 years; male: 49.0%; median follow-up: 9.1 months [interquartile range: 8.0-10.9]), PPIs were associated with higher infection risk (aIRR: 1.11; 95% CI: 1.08-1.15) but not other outcomes. CONCLUSIONS: Although PPI use was associated with a higher COVID-19 risk, severe infection was limited to two-dose but not three-dose vaccine recipients.
RESUMEN
Objective: To analyze the potential value of paraspinal nerve block (PVB) in percutaneous nephrolithotomy (PCNL) and to compare it with general anesthesia and epidural anesthesia. Methods: 120 patients undergoing PCNL surgery in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from January 2021 to June 2022 were selected and divided into PVB anesthesia group, general anesthesia group, and epidural anesthesia group according to different anesthesia methods, with 40 cases in each group. The anesthesia index (anesthesia operation time, anesthetic effect time, anesthesia time), the vital signs (heart rate, mean arterial pressure), postoperative pain [visual analog scale (VAS)], stress response index (cortisol and noradrenaline), the incidence of adverse reactions (nausea and vomiting, lethargy, dizziness, skin itching, bradycardia) were compared among the three groups. Results: The operation time of the anesthesia in the PVB anesthesia group was 5.72±1.25, which was significantly lower than that in the the general (7.95±1.15) and epidural anesthesia groups(8.23±1.43), and the differences were statistically significant (P = .000). The time of onset of anesthesia in the PVB anesthesia group was 6.63±1.87, which was significantly lower than that in the the general (9.84±2.41) and epidural anesthesia groups(10.14±2.89), and the differences were statistically significant (P = .000).The heart rate during percutaneous puncture and intraoperative lithotripsy in the PVB anesthesia group was statistically lower than in the general and epidural anesthesia groups (P < .05). The mean arterial pressure 20 minutes after anesthesia and at the end of operation in the PVB anesthesia group was higher than that in the general anesthesia group, and the mean arterial pressure during percutaneous puncture and intraoperative lithotomy was lower than that in the general anesthesia group (P < .05). The VAS scores of the PVB anesthesia group at 2, 6, 12, 24, and 48 hours after the operation were lower than those of general and epidural anesthesia groups (P < .05). The incidence of adverse reactions was 5.00% (2/40) in the PVB anesthesia group and 35.00% (14/40) in the general anesthesia group, which was lower than that of 27.50% (11/40) in the epidural anesthesia group. (P < .05). Conclusion: The potential value of PVB in PCNL is high is better than that of general anesthesia and epidural anesthesia, anesthesia can shorten operation time and work time, extend the time of anesthesia to maintain, and be helpful to the intraoperative vital signs in patients with stable, mild postoperative pain and stress, low incidence of adverse reactions, efficacy and safety are good, can be introduced.
RESUMEN
Concerns have been raised regarding potential weaker vaccine immunogenicity with higher immune suppression for individuals with pre-existing mental disorders. Yet, data on the effectiveness of COVID-19 vaccinations among this vulnerable population are limited. A case-control study was conducted to investigate the risks of COVID-19-related hospitalisation and mortality among individuals with mental disorders following one to three doses of BNT162b2 and CoronaVac vaccinations in Hong Kong. Data were extracted from electronic health records, vaccination and COVID-19 confirmed case records. Conditional logistic regression was applied with adjustment for comorbidities and medication history. Subgroup analyses were performed with stratification: by age (< 65 and ≥ 65) and mental disorders diagnosis (depression, schizophrenia, anxiety disorder, and bipolar disorder). Two doses of BNT162b2 and CoronaVac significantly reduced COVID-19-related hospitalisation and mortality. Further protection for both outcomes was provided after three doses of BNT162b2 and CoronaVac. The vaccine effectiveness magnitude of BNT162b2 was generally higher than CoronaVac, but the difference diminished after the third dose. Individuals with mental disorders should be prioritised in future mass vaccination programmes of booster doses or bivalent COVID-19 vaccines. Targeted strategies should be developed to resolve the reasons behind vaccine hesitancy among this population and increase their awareness on the benefits of vaccination.
Asunto(s)
COVID-19 , Trastornos Mentales , Humanos , Vacunas contra la COVID-19 , Vacuna BNT162 , COVID-19/prevención & control , Estudios de Casos y Controles , Vacunación , HospitalizaciónRESUMEN
Background: Antibiotics may increase the risk of COVID-19 among non-vaccinated subjects via probable gut dysbiosis. We aimed to investigate whether antibiotics also affect the clinical outcomes of COVID-19 vaccine recipients. Methods: This was a territory-wide cohort study of 3,821,302 COVID-19 vaccine recipients (aged ≥ 18 years) with ≥2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior COVID-19, prior gastrointestinal surgery, and immunocompromised status. The primary outcome was COVID-19 infection and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Exposure was pre-vaccination antibiotic use (within 180 days of first vaccine dose). Covariates included age, sex, Charlson Comorbidity Index, and concomitant medication use. Subjects were followed from the index date (first dose vaccination) until outcome occurrence, death, an additional dose of vaccination, or 15 November 2022. Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with antibiotic use. Results: Among 342,338 PS matched three-dose vaccine recipients (mean age: 57.4 years; male: 45.1%) with a median follow-up of 13.6 months (IQR: 9.2-16.3), antibiotics were associated with a higher risk of COVID-19 infection (aIRR: 1.16;95% CI: 1.14-1.19), hospitalization (aIRR: 1.75;95% CI: 1.65-1.86), and severe infection (aIRR: 1.60; 95% CI: 1.21-2.11). Notably, antibiotic use was associated with a higher risk of severe infection and death among CoronaVac recipients (aIRR: 1.62 95% CI: 1.18-2.22 and aIRR: 2.70, 95% CI: 1.54-4.73 for the two secondary outcomes, respectively), but not BNT162b2 recipients. Conclusions: Pre-vaccination use of antibiotics was associated with a higher risk of COVID-19 infection, hospitalization, and severe disease outcomes.
RESUMEN
BACKGROUND: This study aims to evaluate waning effectiveness against severe and fatal COVID-19 with two to three doses of CoronaVac/BNT162b2, where data are limited. METHODS: A case-control study included individuals aged ≥18 years, unvaccinated or received two to three doses of CoronaVac/BNT162b2, using electronic healthcare databases in Hong Kong. Those with first COVID-19-related hospitalization, severe complications, or mortality between 1 January and 15 August 2022 were defined as cases and matched with up-to-10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness (VE) against COVID-19-related outcomes was estimated at different time intervals from second and third-dose vaccination (0-13 up-to 210-240 days) using conditional logistic regression adjusted for comorbidities and medications. RESULTS: By 211-240 days after second dose, VE against COVID-19-related hospitalization reduced to 46.6% (40.7-51.8%) for BNT162b2 and 36.2% (28.0-43.4%) for CoronaVac, and VE against COVID-19-related mortality were 73.8% (55.9-84.4%) and 76.6% (60.8-86.0%). After third dose, VE against COVID-19-related hospitalization decreased from 91.2% (89.5-92.6%) for BNT162b2 and 76.7% (73.7-79.4%) for CoronaVac at 0-13 days, to 67.1% (60.4-72.6%) and 51.3% (44.2-57.5%) at 91-120 days. VE against COVID-19-related mortality for BNT162b2 remained high from 0-13 days [98.2% (95.0-99.3%)] to 91-120 days [94.6% (77.7-98.7%)], and for CoronaVac reduced from 0-13 days [96.7% (93.2-98.4%)] to 91-120 days [86.4% (73.3-93.1%)]. CONCLUSIONS: Significant risk reduction against COVID-19-related hospitalization and mortality after CoronaVac or BNT162b2 vaccination was observed for >240 and >120 days after second and third doses compared to unvaccinated, despite significant waning over time. Timely administration of booster doses could provide higher levels of protection.
Asunto(s)
Vacuna BNT162 , COVID-19 , Humanos , Adolescente , Adulto , COVID-19/terapia , Estudios de Casos y Controles , HospitalizaciónRESUMEN
BACKGROUND: People with substance use disorder have a high risk of SARS-CoV-2 infection and subsequent poor outcomes. Few studies have evaluated COVID-19 vaccine effectiveness among people with substance use disorder. We aimed to estimate the vaccine effectiveness of BNT162b2 (Fosun-BioNTech) and CoronaVac (Sinovac) against SARS-CoV-2 omicron (B.1.1.529) infection and related hospital admission in this population. METHODS: We did a matched case-control study using electronic health databases in Hong Kong. Individuals diagnosed with substance use disorder between Jan 1, 2016, and Jan 1, 2022, were identified. People aged 18 years and older with SARS-CoV-2 infection from Jan 1 to May 31, 2022, and people with COVID-19-related hospital admission from Feb 16 to May 31, 2022, were included as cases and were matched by age, sex, and previous clinical history with controls from all individuals diagnosed with substance use disorder who attended the Hospital Authority health services: up to three controls for SARS-CoV-2 infection and up to ten controls for hospital admission. Conditional logistical regression was used to evaluate the association between vaccination status (ie, one, two, or three doses of BNT162b2 or CoronaVac) and the risk of SARS-CoV-2 infection and COVID-19-related hospital admission, adjusted for baseline comorbidities and medication use. FINDINGS: Among 57 674 individuals with substance use disorder, 9523 people with SARS-CoV-2 infections (mean age 61·00 years, SD 14·90; 8075 [84·8%] males and 1448 [15·2%] females) were identified and matched to 28 217 controls (mean age 60·99 years, 14·67; 24 006 [85·1%] males and 4211 [14·9%] females), and 843 people with COVID-19-related hospital admissions (mean age 70·48 years, SD 14·68; 754 [89·4%] males and 89 [10·6%] females) were identified and matched to 7459 controls (mean age 70·24 years, 13·87; 6837 [91·7%] males and 622 [8·3%] females). Data on ethnicity were not available. We observed significant vaccine effectiveness against SARS-CoV-2 infection for two-dose BNT162b2 vaccination (20·7%, 95% CI 14·0-27·0, p<0·0001) and three-dose vaccination (all BNT162b2 41·5%, 34·4-47·8, p<0·0001; all CoronaVac 13·6%, 5·4-21·0, p=0·0015; BNT162b2 booster after two-dose CoronaVac 31·3%, 19·8-41·1, p<0·0001), but not for one dose of either vaccine or two doses of CoronaVac. Significant vaccine effectiveness against COVID-19-related hospital admission was detected after one dose of BNT162b2 vaccination (35·7%, 3·8-57·1, p=0·032), two-dose vaccination (both BNT162b2 73·3%, 64·3 to 80·0, p<0·0001; both CoronaVac 59·9%, 50·2-67·7, p<0·0001), and three-dose vaccination (all BNT162b2 86·3%, 75·6-92·3, p<0·0001; all CoronaVac 73·5% 61·0-81·9, p<0·0001; BNT162b2 booster after two-dose CoronaVac 83·7%, 64·6-92·5, p<0·0001), but not after one dose of CoronaVac. INTERPRETATION: For both BNT162b2 and CoronaVac, two-dose or three-dose vaccination was protective against COVID-19-related hospital admission and the booster dose provided protection against SARS-CoV-2 infection among people with substance use disorder. Our findings confirm the importance of booster doses in this population during the period dominated by the omicron variant. FUNDING: Health Bureau, the Government of the Hong Kong Special Administrative Region.
Asunto(s)
COVID-19 , Trastornos Relacionados con Sustancias , Femenino , Masculino , Humanos , Persona de Mediana Edad , Anciano , Vacunas contra la COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Vacuna BNT162 , Estudios de Casos y Controles , SARS-CoV-2 , Hong Kong/epidemiología , Eficacia de las Vacunas , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/terapia , HospitalesRESUMEN
Background COVID-19 vaccines have demonstrated effectiveness against SARS-CoV-2 infection, hospitalization, and mortality. The association between vaccination and risk of cardiovascular complications shortly after SARS-CoV-2 infection among patients with cardiovascular disease remains unknown. Methods and Results A case-control study was conducted with cases defined as patients who had myocardial infarction or stroke within 28 days after SARS-CoV-2 infection between January 1, 2022 and August 15, 2022. Controls were defined as all other patients who attended any health services and were not cases. Individuals without history of cardiovascular disease were excluded. Each case was randomly matched with 10 controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Adjusted odds ratio with 95% CI was estimated using conditional logistic regression. We identified 808 cases matched with 7771 controls among all patients with cardiovascular disease. Results showed that vaccination with BNT162b2 or CoronaVac was associated with a lower risk of myocardial infarction or stroke after SARS-CoV-2 infection with a dose-response relationship. For BNT162b2, risk decreased from 0.49 (95% CI, 0.29-0.84) to 0.30 (95% CI, 0.20-0.44) and 0.17 (95% CI, 0.08-0.34) from 1 to 3 doses, respectively. Similar trends were observed for CoronaVac, with risk decreased from 0.69 (95% CI, 0.57-0.85) to 0.42 (95% CI, 0.34-0.52) and 0.32 (95% CI, 0.21-0.49) from 1 to 3 doses, respectively. Conclusions Vaccination with BNT162b2 or CoronaVac is associated with a lower risk of myocardial infarction or stroke after SARS-CoV-2 infection among patients with cardiovascular disease.
Asunto(s)
COVID-19 , Enfermedades Cardiovasculares , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Enfermedades Cardiovasculares/epidemiología , Vacunas contra la COVID-19/efectos adversos , Vacuna BNT162 , Estudios de Casos y Controles , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Infarto del Miocardio/epidemiología , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Vacunación/efectos adversosRESUMEN
AIMS: Patients with atrial fibrillation (AF) have a higher risk of ischaemic stroke or systemic embolism, with a greater risk for female patients. This study aims to evaluate the risk of ischaemic stroke or systemic embolism and bleeding following COVID-19 vaccination in patients with AF and the sex differences. METHODS AND RESULTS: Self-controlled case series (SCCS) analysis was conducted to evaluate the risk of ischaemic stroke or systemic embolism and bleeding following BNT162b2 or CoronaVac in patients with AF, using the territory-wide electronic medical records from the Hospital Authority and vaccination records from the Department of Health in Hong Kong. Patients with a primary diagnosis of ischaemic stroke, systemic embolism, or bleeding in the inpatient setting between 23 February 2021 and 31 March 2022 were included. A nested case-control analysis was also conducted with each case randomly matched with 10 controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Conditional Poisson regression was used in the SCCS analysis, and conditional logistic regression was used in the nested case-control analysis to assess the risks, and all analyses were stratified by sex and type of vaccines. Among 51 158 patients with AF, we identified an increased risk of ischaemic stroke or systemic embolism after the first dose of BNT162b2 in SCCS analysis during 0-13 days [incidence rate ratio 6.60, 95% confidence interval (CI) 1.51-28.77] and 14-27 days (6.53, 95% CI 1.31-32.51), and nested case-control analysis during 0-13 days (adjusted odds ratio 6.21, 95% CI 1.14-33.91) and 14-27 days (5.52, 95% CI 1.12-27.26) only in female patients. The increased risk in female patients following the first dose of CoronaVac was only detected during 0-13 days (3.88, 95% CI 1.67-9.03) in the nested case-control analysis. No increased risk of ischaemic stroke or systemic embolism was identified in male patients, and no increased risk of bleeding was detected in all patients with AF for both vaccines. An increased risk of ischaemic stroke or systemic embolism after COVID-19 was also observed in both females (17.42, 95% CI 5.08-59.73) and males (6.63, 95% CI 2.02-21.79). CONCLUSIONS: The risk of ischaemic stroke or systemic embolism after COVID-19 vaccination was only increased in female patients with AF. However, as the risk after COVID-19 was even higher, proactive uptake of COVID-19 vaccines is recommended to prevent the potential severe outcomes after infection.
Asunto(s)
Fibrilación Atrial , Isquemia Encefálica , COVID-19 , Embolia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Vacunas contra la COVID-19/efectos adversos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Vacuna BNT162 , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiología , Isquemia Encefálica/etiología , Estudios de Casos y Controles , Caracteres Sexuales , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/prevención & control , Embolia/prevención & control , Hemorragia , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/etiología , Vacunación/efectos adversosRESUMEN
BACKGROUND: Multimorbidity is a prevalent risk factor for COVID-19-related complications and death. We sought to evaluate the association of homologous booster vaccination using BNT162b2 (Pfizer-BioNTech) or CoronaVac (Sinovac) with COVID-19-related deaths among people with multimorbidity during the initial Omicron wave of the COVID-19 pandemic. METHODS: Using routine clinical records from public health care facilities in Hong Kong, we conducted a territory-wide retrospective cohort study comparing people aged 18 years or older with 2 or more chronic conditions who received a homologous booster (third) dose with those who received only 2 doses, between Nov. 11, 2021, and Mar. 31, 2022. The primary outcome was death related to COVID-19. RESULTS: We included 120 724 BNT162b2 recipients (including 87 289 who received a booster), followed for a median of 34 (interquartile range [IQR] 20-63) days and 127 318 CoronaVac recipients (including 94 977 who received a booster), followed for a median of 38 (IQR 22-77) days. Among BNT162b2 recipients, booster-vaccinated people had fewer COVID-19-related deaths than those who received 2 doses (5 v. 34, incidence rate 1.3 v. 23.4 per million person-days, weighted incidence rate ratio [IRR] 0.05, 95% confidence interval [CI] 0.02-0.16). We observed similar results among recipients of CoronaVac booster vaccination compared with those who received only 2 doses (26 v. 88, incidence rate 5.3 v. 53.1 per million person-days, weighted IRR 0.08, 95% CI 0.05-0.12). INTERPRETATION: Among people with multimorbidity, booster vaccination with BNT162b2 or CoronaVac was associated with reductions of more than 90% in COVID-19-related mortality rates compared with only 2 doses. These results highlight the crucial role of booster vaccination for protecting vulnerable populations as the COVID-19 pandemic continues to evolve.
Asunto(s)
COVID-19 , Vacunas de ARNm , Humanos , Vacuna BNT162 , Estudios de Cohortes , Multimorbilidad , Pandemias , Estudios Retrospectivos , COVID-19/prevención & control , VacunaciónRESUMEN
BACKGROUND: Risk of suicide attempt, depression, anxiety and seizure and the association with statins is an ongoing debate. We aim to investigate the association between statins and the above neuropsychological outcomes, in specific pre- and post-exposure time windows. METHODS: We identified patients aged 40-75 years old who were dispensed a statin between January 1, 2003 and December 31, 2012 from the Hong Kong Clinical Data Analysis & Reporting System (CDARS), an electronic medical records database. Patients with new onset of suicide attempt, depression, anxiety and seizure were derived from the original dataset separately, in a self-controlled case series study design. A non-parametric spline-based self-controlled case series model was built to measure continuous changes of risk. RESULTS: We identified 396,614 statin users. The risk of each outcome was elevated prior to statin initiation with incidence rate ratios of 1.38 (95 % CI, 1.09-1.74) for suicide attempt, 1.29 (95 % CI, 1.15-1.45) for depression, 1.35 (95 % CI, 1.19-1.53) for anxiety, and 1.45 (95 % CI, 1.21-1.73) for seizure. The incidence rate ratios remained elevated after the initiation of statins during the first 90 and 91-365 days after statin prescription and decreased to the baseline level after 1 year of continuous prescription. LIMITATIONS: CDARS includes prescription data but not adherence data, which could lead to misclassification of exposure periods. CONCLUSIONS: Our study does not support a direct association between statin use and suicide attempt, depression, anxiety and seizure, whose risks could be explained by cardiovascular events, for which statins were prescribed.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Adulto , Persona de Mediana Edad , Anciano , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Intento de Suicidio/prevención & control , Depresión/tratamiento farmacológico , Depresión/epidemiología , Convulsiones/epidemiología , Ansiedad/tratamiento farmacológico , Ansiedad/epidemiologíaRESUMEN
Background: COVID-19 vaccines are important for patients with heart failure (HF) to prevent severe outcomes but the safety concerns could lead to vaccine hesitancy. This study aimed to investigate the safety of two COVID-19 vaccines, BNT162b2 and CoronaVac, in patients with HF. Methods: We conducted a self-controlled case series analysis using the data from the Hong Kong Hospital Authority and the Department of Health. The primary outcome was hospitalization for HF and the secondary outcomes were major adverse cardiovascular events (MACE) and all hospitalization. We identified patients with a history of HF before February 23, 2021 and developed the outcome event between February 23, 2021 and March 31, 2022 in Hong Kong. Incidence rate ratios (IRR) were estimated using conditional Poisson regression to evaluate the risks following the first three doses of BNT162b2 or CoronaVac. Findings: We identified 32,490 patients with HF, of which 3035 were vaccinated and had a hospitalization for HF during the observation period (BNT162b2 = 755; CoronaVac = 2280). There were no increased risks during the 0-13 days (IRR 0.64 [95% confidence interval 0.33-1.26]; 0.94 [0.50-1.78]; 0.82 [0.17-3.98]) and 14-27 days (0.73 [0.35-1.52]; 0.95 [0.49-1.84]; 0.60 [0.06-5.76]) after the first, second and third doses of BNT162b2. No increased risks were observed for CoronaVac during the 0-13 days (IRR 0.60 [0.41-0.88]; 0.71 [0.45-1.12]; 1.64 [0.40-6.77]) and 14-27 days (0.91 [0.63-1.32]; 0.79 [0.46-1.35]; 1.71 [0.44-6.62]) after the first, second and third doses. We also found no increased risk of MACE or all hospitalization after vaccination. Interpretation: Our results showed no increased risk of hospitalization for HF, MACE or all hospitalization after receiving BNT162b2 or CoronaVac vaccines in patients with HF. Funding: The project was funded by a Research Grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (Ref. No. COVID19F01). F.T.T.L. (Francisco T.T. Lai) and I.C.K.W. (Ian C.K. Wong)'s posts were partly funded by the D24H; hence this work was partly supported by AIR@InnoHK administered by Innovation and Technology Commission.
RESUMEN
BACKGROUND: With accruing case reports on de novo or relapsing glomerular diseases (GD) following different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we evaluated the risk of GD following BNT162b2 and CoronaVac vaccines. METHODS: A modified self-controlled case series analysis was conducted using anonymized, territory-wide SARS-CoV-2 vaccination records in Hong Kong. All Hong Kong residents aged 18 years or above with outcomes of interest were included. Outcomes of interest were GD, proteinuria or hematuria within 42 days following each dose of SARS-CoV-2 vaccines. Incidence per 100 000 doses of SARS-CoV-2 vaccines administered was calculated, and incidence rate ratios (IRRs) were estimated using conditional Poisson regression with seasonality adjustment. RESULTS: Between 23 February 2021 and 31 March 2022, 4062 patients had an incident diagnosis of GD, proteinuria or hematuria, with 2873 of them being vaccinated during the observation period. The incidences of the composite events 1-41 days after vaccination were 3.7 (95% CI 3.1-4.4) per 100 000 doses of BNT162b2 administered, and 6.5 (95% CI 5.7-7.5) per 100 000 doses CoronaVac administered. There was no significant increase in the risks of composite events following the first (BNT162b2: IRR = 0.76, 95% CI 0.56-1.03; CoronaVac: IRR = 0.92, 95% CI 0.72-1.19), second (BNT162b2: IRR = 0.92, 95% CI 0.72-1.17; CoronaVac: IRR = 0.88. 95% CI 0.68-1.14) or third (BNT162b2: IRR = 0.39. 95% CI 0.15-1.03; CoronaVac: IRR = 1.18. 95% CI 0.53-2.63) dose of SARS-CoV-2 vaccines. CONCLUSIONS: There was no evidence of increased risks of de novo or relapsing GD with either BNT162b2 or CoronaVac vaccines.
Asunto(s)
COVID-19 , Enfermedades Renales , Humanos , Vacunas contra la COVID-19 , Vacuna BNT162 , Hematuria , ARN Mensajero , SARS-CoV-2 , ProteinuriaRESUMEN
BACKGROUND AND OBJECTIVE: Evidence of the effectiveness of statins compared with fibrates for primary prevention of cardiovascular events is limited. Therefore, we assessed the comparative effectiveness of simvastatin versus gemfibrozil for primary prevention of major adverse cardiovascular events (MACE) and mortality. METHODS: This territory-wide cohort study used electronic health records of simvastatin and gemfibrozil prescriptions from the Hong Kong Hospital Authority and compared simvastatin or gemfibrozil initiation. The primary outcome was MACE, defined as the composite of the first diagnosis of cardiovascular mortality, coronary heart disease, or stroke. Secondary outcomes were the individual components of MACE, all-cause mortality, and non-cardiovascular mortality. Inverse probability of treatment weighting on the propensity score was used to estimate hazard ratios (HRs). RESULTS: A total of 223,699 individuals (120,207 [53.7%] women; median follow-up 7.0 years [interquartile range 5.7-9.1]) who were prescribed simvastatin (n = 168,630) or gemfibrozil (n = 55,069) were included. Simvastatin was associated with a reduced risk of MACE (HR 0.90, 95% confidence interval [CI] 0.88-0.93), all-cause mortality (HR 0.88, 95% CI 0.86-0.90), cardiovascular mortality (HR 0.71, 95% CI 0.67-0.76), and non-cardiovascular mortality (HR 0.92, 95% CI 0.89-0.95). Associations for MACE varied according to baseline characteristics with gemfibrozil being associated with a reduced risk of MACE in men and patients with low baseline high-density lipoprotein (HDL) cholesterol (< 1.0 mmol/L). CONCLUSION: The results of this study showed better population-level effectiveness of simvastatin compared with gemfibrozil for the primary prevention of MACE; however, a definitive randomized controlled trial is required to compare simvastatin with gemfibrozil among patients with low HDL cholesterol, as they appear to obtain benefit with gemfibrozil.
Asunto(s)
Enfermedad Coronaria , Gemfibrozilo , Masculino , Humanos , Femenino , Gemfibrozilo/uso terapéutico , Simvastatina/uso terapéutico , Estudios de Cohortes , Estudios Retrospectivos , Enfermedad Coronaria/inducido químicamente , Enfermedad Coronaria/prevención & control , Prevención Primaria , Atención Primaria de SaludRESUMEN
Data regarding protection against mortality and severe complications after Omicron BA.2 infection with CoronaVac and BNT162b2 vaccines remains limited. We conducted a case-control study to evaluate the risk of severe complications and mortality following 1-3 doses of CoronaVac and BNT162b2 using electronic health records database. Cases were adults with their first COVID-19-related mortality or severe complications between 1 January and 31 March 2022, matched with up-to 10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness against COVID-19-related mortality and severe complications by type and number of doses was estimated using conditional logistic regression adjusted for comorbidities and medications. Vaccine effectiveness (95% CI) against COVID-19-related mortality after two doses of BNT162b2 and CoronaVac were 90.7% (88.6-92.3) and 74.8% (72.5-76.9) in those aged ≥65, 87.6% (81.4-91.8) and 80.7% (72.8-86.3) in those aged 50-64, 86.6% (71.0-93.8) and 82.7% (56.5-93.1) in those aged 18-50. Vaccine effectiveness against severe complications after two doses of BNT162b2 and CoronaVac were 82.1% (74.6-87.3) and 58.9% (50.3-66.1) in those aged ≥65, 83.0% (69.6-90.5) and 67.1% (47.1-79.6) in those aged 50-64, 78.3% (60.8-88.0) and 77.8% (49.6-90.2) in those aged 18-50. Further risk reduction with the third dose was observed especially in those aged ≥65 years, with vaccine effectiveness of 98.0% (96.5-98.9) for BNT162b2 and 95.5% (93.7-96.8) for CoronaVac against mortality, 90.8% (83.4-94.9) and 88.0% (80.8-92.5) against severe complications. Both CoronaVac and BNT162b2 vaccination were effective against COVID-19-related mortality and severe complications amidst the Omicron BA.2 pandemic, and risks decreased further with the third dose.
Asunto(s)
Vacuna BNT162 , COVID-19 , Adulto , COVID-19/prevención & control , Estudios de Casos y Controles , Humanos , SARS-CoV-2 , VacunaciónRESUMEN
Tripartite motif-containing protein 11 (TRIM11) and family with sequence similarity 46B (FAM46B) have been demonstrated to play roles in prostate cancer development, but their function in paclitaxel resistance remains unclear. The role of TRIM11 and FAM46B in paclitaxel resistance in prostate cancer was estimated. The paclitaxel-resistant cells were established with gradually increasing concentrations of paclitaxel in prostate cancer cells. The sensitivity to paclitaxel of established cells was assessed by the value of the median inhibitory concentration in the presence of 0-1000 nM paclitaxel. The expression level of TRIM11 and FAM46B was evaluated by real-time quantitative polymerase chain reaction. The proliferation, migration, and invasion of established cells were evaluated by CCK8 and Tran-swell assay. TRIM11 was upregulated in paclitaxel-resistant cells and promoted the proliferation, migration, and invasion of established cells. The significant downregulation of FAM46B was observed in paclitaxel-resistant cells. Although the overexpression of FAM46B suppressed the viability and metastasis of paclitaxel-resistant cells, which was reversed by the upregulation of TRIM11. Both the knockdown of TRIM11 and overexpression of FAM46B could enhance paclitaxel sensitivity of established resistant cells. The promoted effect of FAM46B overexpression was alleviated by the elevation of TRIM11. TRIM11 could improve the sensitivity to paclitaxel of resistant prostate cancer cells via regulating FAM46B.
Asunto(s)
Paclitaxel , Neoplasias de la Próstata , Línea Celular Tumoral , Proliferación Celular , Resistencia a Antineoplásicos/genética , Humanos , Masculino , Paclitaxel/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Proteínas de Motivos Tripartitos/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
AIMS: Concern about the cardiovascular safety of coronavirus disease 2019 (COVID-19) vaccines among individuals with cardiovascular disease (CVD) may lead to vaccine hesitancy. We sought to assess the association between two COVID-19 vaccines, BNT162b2 and CoronaVac, and the risk of major adverse cardiovascular events (MACE) in individuals with established CVD. METHODS AND RESULTS: We identified individuals with a history of CVD before 23 February 2021 and a diagnosis of MACE between 23 February 2021 and 31 January 2022 in Hong Kong. MACE was defined as a composite of myocardial infarction, stroke, revascularization, and cardiovascular death. Electronic health records from the Hong Kong Hospital Authority were linked to vaccination records from the Department of Health. A self-controlled case-series method was used to evaluate the risk of MACE for 0-13 and 14-27 days after two doses of COVID-19 vaccine. We estimated incidence rate ratios (IRRs) to compare the risk of MACE between each risk period and the baseline period. A total of 229 235 individuals with CVD were identified, of which 1764 were vaccinated and had a diagnosis of MACE during the observation period (BNT162b2 = 662; CoronaVac = 1102). For BNT162b2, IRRs were 0.48 [95% confidence interval (CI) 0.23-1.02] for the first dose and 0.87 (95% CI 0.50-1.52) for the second dose during the 0-13 days risk period, 0.40 (95% CI 0.18-0.93) for the first dose and 1.13 (95% CI 0.70-1.84) for the second dose during the 14-27 days risk period. For CoronaVac, the IRRs were 0.43 (95% CI 0.24-0.75) for the first dose and, 0.73 (95% CI 0.46-1.16) for the second dose during the 0-13 days risk period, 0.54 (95% CI 0.33-0.90) for the first dose and 0.83 (95% CI 0.54-1.29) for the second dose during the 14-27 days risk period. Consistent results were found in subgroup analyses for different sexes, age groups and different underlying cardiovascular conditions. CONCLUSION: Our findings showed no evidence of an increased risk of MACE after vaccination with BNT162b2 or CoronaVac in patients with CVD. Future research is required to monitor the risk after the third dose of each vaccine.